Recurrent spontaneous abortion, defined as three or more unexplained pregnancy losses prior to 20 weeks of gestation, occurs in approximately 0.3% of couples who desire children (Stirrat, Lancet 336:728-733 (1990)). Among the factors identified as causing this disorder are: genetic or chromosomal abnormalities (3-5% of cases); endocrine etiologies (17%); infections (5%); and mularian anomalies (10%). The etiology of the remaining 50-60% of miscarriages is uncertain, but there are reasons to suspect that immunological factors may play a role.
Pregnancy is accompanied by a decline in the reactivity of maternal T-cells to HLA antigens (Tafuri, et al., Science 270:630-633 (1995)) and by a diminished immunological responsiveness of the mother (see e.g., Brunham et al., J. Clin. Invest. 72:1629-1638 (1983); Muchmore et al., J. Immunol. 138:2547-2553 (1987); and Tartof, Clin. Exp. Immunol. 57:502-510 (1984)). This suggests that maternal immunological changes may help provide an environment conducive to fetal development.
Additional evidence comes from observations made in patients with immunological disorders. Women with rheumatoid arthritis (RA), generally experience an improvement in their symptoms during pregnancy (Cecere, et al., Clin. Rheum. Dis. 7:747-768 (1981) This may be related to the down-regulation of tumor necrosis factor alpha, a cytokine suspected of contributing to the severity of RA (Stalimach, et al., Lab. Invest. 73:384-392 (1995)). In contrast, women with systemic lupus erythematosus (SLE) often experience a worsening of the disease when they become pregnant (Nelson, Arthritis Rheum. 139:191-194 (1996)). Diminished interleukin-2 production in response to recall antigens correlates with SLE disease activity and disease flares (Bermas, et al., J. Clin. Immunol. 14:169-177 (1994)). Since a similar decrease is also seen during normal pregnancy, this may explain why pregnant women with SLE experience an exacerbation of their symptoms.
Although immunological changes have been associated with pregnancy, the extent to which these changes are necessary for a successful completion of gestation has not been established. A test which correlates pregnancy outcome with a readily measurable immunological parameter would represent a clear advance in reproductive biology and would be of benefit in clinical practice. Ideally, such a test would be simple to perform and effective for the majority of pregnant women.